A Dose Escalation Trial of Radiation Therapy (RT) for Hepatocellular Carcinoma (HCC)
A Phase I Dose Escalation Trial of Conformal Hypofractionated Radiation Therapy for Patients With Hepatitis B Virus-Related Child A Cirrhosis and Hepatocellular Carcinoma
1 other identifier
interventional
20
1 country
1
Brief Summary
Hepatocellular carcinoma (HCC) is one of the leading malignancies in Taiwan. Surgery and local ablative therapy remain the treatment of choice for curative purpose. Transarterial chemoembolization has been the mainstay of intrahepatic control for patients not being candidates for local modalities of treatment. Sorafenib is recently integrated into the treatment options, mainly for intrahepatic or extrahepatic wide spread disease contraindicated for the other modalities. External radiotherapy (RT) has been selectively used for patients with the localized hepatic tumor(s) refractory to the above treatment options. The data from the retrospective studies were biased by the patient selection and uncontrolled comparison with patients not receiving RT. The obstacles for RT to HCC remain unanswered with heterogeneity in dose of radiation and lower tolerance of liver to RT in viral hepatitis carriers. Such a sublethal dose might be associated with unsatisfactory tumor control, intra-/extra-hepatic metastasis, and radiation-induced liver disease in a significant proportion of HCC patients. The purposes of this phase I study are primarily to determine the maximally tolerated dose of RT, and secondarily to evaluate the tumor control, to assess patterns of failure and survival, to analyze the characteristics of radiation-induced liver disease, as well as to collect blood samples for translational research. HCC patients who are hepatitis B virus carriers and graded as Child-Pugh A cirrhosis are enrolled. This dose escalation trial is conducted with the 7-Gy increase in 2 fractions (3.5 Gy per fraction) for a total of four levels, from 42 Gy up to 63 Gy. Conformal RT with three-dimensional design, intensity modulated RT, or volumetric modulated arc therapy is used with the defined dose-volume threshold for normal liver and the other structures. Five patients are treated for each dose level, with dose limiting toxicity in less than 2 patients judged to be acceptable. A minimum of 15 patients are required for the starting dose level of 49 Gy if the treated tumor diameter is less than 10 cm. Imaging modalities are used for estimating treatment response and detecting metastasis. Serum analyses are done for evaluating hepatic function, viral load, hematological toxicity, and translational research for angiogenic and inflammatory studies.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1 hepatocellular-carcinoma
1 active site
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Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 13, 2009
CompletedFirst Posted
Study publicly available on registry
August 17, 2009
CompletedStudy Start
First participant enrolled
September 1, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2011
CompletedOctober 15, 2009
October 1, 2009
1.9 years
August 13, 2009
October 13, 2009
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Maximally tolerated dose of RT
weekly during radiotherapy
Secondary Outcomes (1)
Tumor control, patterns of failure and survival
Monthly after radiotherapy
Study Arms (4)
Dose Level I
EXPERIMENTAL42 Gy in 12 fractions.
Dose Level II
EXPERIMENTAL49 Gy in 14 fractions.
Dose Level III
EXPERIMENTAL56 Gy in 16 fractions.
Dose Level IV
EXPERIMENTAL63 Gy in 18 fractions.
Interventions
All enrolled patients will receive 3.5 Gy per fraction (five fractions per week) at the following levels; Dose escalation by 7 Gy in 2 fractions to maximum of 63 Gy, as follows: Dose Level I: 3.5 Gy for 12 fractions (42 Gy total) Dose Level II: 3.5 Gy for 14 fractions (49 Gy total) Dose Level III: 3.5 Gy for 16 fractions (56 Gy total) Dose Level VI: 3.5 Gy for 18 fractions (63 Gy total)
Eligibility Criteria
You may qualify if:
- Eligible patients include those with HCC based on the diagnostic criteria of European Association for the Study of the Liver (EASL), either confirmed cyto-histologically or confirmed non-invasively (restricted to cirrhotic patients) by radiological criteria (two coincident imaging techniques and focal lesion \> 2 cm with arterial hypervascularization) or combined criteria (one imaging technique associated with AFP, focal lesion \> 2 cm with arterial hypervascularization, and AFP levels \> 400 ng/ml).
- They have Child-Pugh grade A cirrhosis and are HBsAg-positive for more than 6 months.
- These patients are not feasible for other conventional treatment modalities of treatment including surgery, transarterial embolization, ethanol injection, and radiofrequency ablation.
- No systemic anti-cancer therapy with high priority is available.
- All of the above 3 criteria should be judged by the caring physician.
- All intrahepatic disease must be encompassed within the radiation fields, except intrahepatic diseases outside the radiation field(s) have been controlled by other treatment modalities before radiotherapy.
- Karnofsky Performance Scale ≧ 80.
- Age \> 18.
- Adequate bone marrow function, defined as follows:
- Absolute neutrophil count (ANC) \> 1,000 cells/mm3 based upon CBC/differential obtained within 2 weeks prior to registration on study
- Platelets \> 20,000 cells/mm3 based upon CBC/differential obtained within 2 weeks prior to registration on study
- Hemoglobin \> 8.0 g/dl based upon CBC/differential obtained within 2 weeks prior to registration on study (Note: The use of blood transfusion or other intervention to achieve Hgb \> 8.0 g/dl is acceptable.)
- Previous liver resection, embolization, or ablative therapy is permitted.
- Chemotherapy and/or targeted agent therapy must be completed at least 2 weeks prior to radiation.
- Women of childbearing potential and male participants must practice adequate contraception.
- +5 more criteria
You may not qualify if:
- Prior invasive malignancy, other than HCC, (except nonmelanomatous skin cancer) unless disease free for a minimum of 3 years (For example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible).
- Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.
- Tumor thrombosis in the main trunk of portal vein, hepatic vein, or inferior vena cava.
- Child-Pugh grade B or C cirrhosis.
- Extrahepatic metastasis.
- Clinical ascites that requires diuretic treatment or paracentesis for symptom relief.
- Serum alanine aminotransferase (ALT) level \> 5X normal upper limits or total bilirubin level \> 3.0.
- Active hepatitis (serum ALT level \> 5X normal upper limits) or clinically significant liver failure.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Taiwan University Hospital
Taipei, 100, Taiwan
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jason Chia-Hsien Cheng, Ph.D.
National Taiwan University Hospital
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
Study Record Dates
First Submitted
August 13, 2009
First Posted
August 17, 2009
Study Start
September 1, 2009
Primary Completion
August 1, 2011
Last Updated
October 15, 2009
Record last verified: 2009-10